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Ripples from neighbouring transcription

Nature Cell Biology volume 10, pages 11061113 (2008) | Download Citation

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Abstract

Transcriptional initiation of each gene is assumed to be independently controlled in mammals. On the other hand, recent large-scale transcriptome analyses have shown that the genome is pervasively transcribed, such that the most of its DNA gives rise to RNAs1,2,3,4. This raises the question of whether it is possible to pinpoint and activate a particular locus without perturbing numerous neighbouring transcripts. Here we show that intensive transcription at one locus frequently spills over into its physical neighbouring loci. Rapid induction of immediate-early genes (IEGs) in response to growth factor stimulation5 is accompanied by co-upregulation of their neighbouring genes. Profiling the primary transcripts in the nucleus with whole-genome tiling arrays delineated simultaneous activation of transcription centred on IEGs. Even in surrounding intergenic regions, transcriptional activation took place at the same time. Acetylation levels of histone H3 and H4 are elevated along with the IEG induction and neighbouring co-upregulation. Inhibition of the mitogen-activated protein kinase (MAPK) pathway or the transcription factor SRF suppresses all transcriptional upregulation. These results suggest that transcriptional activation has a ripple effect, which may be advantageous for coordinated expression.

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Acknowledgements

We thank I. Smith for helpful discussion and M. McMahon for ΔB-Raf–ER cells. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to E.N.).

Author information

Affiliations

  1. Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.

    • Miki Ebisuya
    • , Takuya Yamamoto
    • , May Nakajima
    •  & Eisuke Nishida

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Contributions

M.E. conceived the study and wrote the manuscript with the help of E.N.; M.E. and T.Y. designed and performed the experiments and analysed the data; M.N. conducted histone acetylation ChIP experiments; E.N. supervised the project.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Eisuke Nishida.

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    Supplementary Information

    Supplementary Figures S1, S2, S3, S4, S5, Supplementary Tables 1, 2, 3, 4 and 5

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DOI

https://doi.org/10.1038/ncb1771

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